Neurodegenerative diseases affect the quality of life for a significant amount of the population, ranging from children to the elderly. Not much is known regarding the causes of this class of diseases, making the approach towards effective therapies difficult. Pathways involved in neurodegeneration include oxidative stress, synaptic dysfunction, and altered gene expression. This research proposal focuses on the interplay between these pathways through the study of microtubule function. The specific mechanisms causing transcriptional alterations observed in neurodegenerative disorders, such as Parkinson's disease, are yet to be elucidated;however a potential mechanism involves alterations of microtubule function. Increasing evidence of dysfunction in microtubule-dependent processes is being found in neurodegenerative diseases - suggesting it as a common mechanism underlying neuronal degeneration. This research proposal examines if specific regulatory changes in the microtubule network in oxidatively- stressed neurons might impact efficiency of processes such as transcription factor trafficking and neurite remodeling. Techniques in molecular biology, biochemistry, and imaging will be employed to address these questions. Aim 1 will examine neuronal microtubule dynamics in response to oxidative injury via live-cell imaging and Aim 2 will examine the effects of oxidative neuronal injury on microtubule post-translational modifications and binding of molecular motors. Both aims will further examine the effects of oxidative modulations in microtubule function on transcription factor trafficking and neurite maintenance. In addition to providing predoctoral training to the applicant, this research proposal will help elucidate mechanisms that lead to neuronal degeneration, which will aid in the development of future neuroprotective strategies. PUBLIC HEALTH RELEVANCE: Neurodegenerative disorders, such as Parkinson's disease, affect the quality of life for a significant amount of the population and are becoming even a greater concern as the U.S. population ages. Elucidating the mechanisms that lead to neuronal dysfunction and degeneration in these disorders will help in the development of future neuroprotective strategies.